Method And Apparatus For Spray Processing Of Porous Medical Devices

ABSTRACT

Thermal spray processing and cold spray processing are utilized to manufacture porous starting materials (such as tube stock, wire and substrate sheets) from biocompatible metals, metal alloys, ceramics and polymers that may be further processed into porous medical devices, such as stents. The spray processes are also used to form porous coatings on consolidated biocompatible medical devices. The porous substrates and coatings may be used as a reservoir to hold a drug or therapeutic agent for elution in the body. The spray-formed porous substrates and coatings may be functionally graded to allow direct control of drug elution without an additional polymer topcoat. The spray processes are also used to apply the drug or agent to the porous substrate or coating when drug or agent is robust enough to withstand the temperatures and velocities of the spray process with minimal degradation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/582,703, filed on Oct. 17, 2006, which is a divisional of U.S.application Ser. No. 10/331,838, filed Dec. 30, 2002 (U.S. Pat. No.7,163,715), which is a continuation-in-part of U.S. application Ser. No.09/880,514, filed Jun. 12, 2001, the contents of each of which arehereby incorporated herein by reference.

BACKGROUND OF THE INVENTION

This invention relates to medical devices, and more particularly tomethods of manufacturing and coating medical devices utilizing thermalspray processing and cold spray processing. The medical devices may bemade porous to act as a functional drug delivery vehicle.

Several interventional treatment modalities are presently used for heartdisease, including balloon and laser angioplasty, atherectomy, andby-pass surgery. A focus of recent development work in the treatment ofheart disease has been directed to endoprosthetic devices referred to asstents. Stents are generally cylindrically shaped intravascular devicesthat are placed within an artery to hold it open. The device can be usedto reduce the likelihood of restenosis and to maintain the patency of ablood vessel immediately after intravascular treatment. In somecircumstances, a stent can also be used as the primary treatment devicewhere the stent is expanded to dilate a stenosis and then left in place.

Many medical devices, including stents, are manufactured fromcommercially available metals and metal alloy substrates, such asstainless steel and cobalt based alloys, configured as tube stock,wherein the substrate typically has average grain sizes ranging fromapproximately 0.0025 inch (64 microns), ASTM grain size 5, to around0.00088 inch (22 microns), ASTM grain size 8. These grain sizestypically result in about two to five grains across the thickness of thedevice. Part of the limitation in achieving a finer grain size withmetals and metal alloys arises from the number of draws and anneals thesubstrate must go through to achieve its final size. Stents and othermedical devices (such as guide wires, ring markers, pacemaker lead tips,and catheters) may benefit from a reduction in grain size of thesubstrate.

Intravascular interventional devices, such as stents, are typicallyimplanted within a vessel in a contracted state, and expanded when inplace in the vessel in order to maintain the patency of the vessel. Suchmedical devices may have a metallic support structure to provide thestrength required to maintain the patency of the vessel in which it isto be implanted so as to allow fluid flow through the vessel. Suchmetallic medical devices are often provided with an exterior surfacecoating with the purpose of providing a more biocompatible and/orhemocompatible surface. Since it is often useful to provide localizedtherapeutic pharmacological treatment of a blood vessel at the locationbeing treated with the medical device, it has been the practice withinthe medical industry to configure such implantable medical devices witha coating of a polymeric material having the capability of being loadedwith antiproliferative drugs and other therapeutic agents. Such polymercoated medical devices provide for the placement and release oftherapeutic drugs at a specific intravascular site, but are relativelyexpensive and difficult to manufacture using conventional processes.

What has been needed and heretofore unavailable in the art ofmanufacturing medical devices, such as stents, configured fromcommercially available biocompatible materials, such as stainless steeland cobalt-based alloys, are methods for forming porous implantablemedical devices and for forming a porous coating on consolidated medicaldevices. In addition, it would be desirable to form drug-eluting medicaldevices without the need for coating the substrate with a polymer. Thepresent invention meets these and other needs.

SUMMARY OF THE INVENTION

The present invention relates to methods of manufacturing porous medicaldevices utilizing thermal spray processing and cold spray processing.Conventional spray processes are adapted to manufacture poroussubstrates and coatings that may be constructed as tube stock, metallicsheet, wire or near net-shaped configurations for forming drug-elutingmedical devices, such as, but not limited to, stents, anastomosis clips,embolic protection filters, graft attachment systems, ring markers,guide wires, mitral valve repair devices, tubular or wire basedimplants, defibrillator or pacemaker lead tips, and catheters or otherdelivery system devices. As part of the spray process or as a separateaspect of the method of manufacture of the medical device, a therapeuticagent or drug may be applied to the porous coating or substrate.

Thermal spray processing and spray processing provide methods formanufacturing a porous medical device for use as a drug delivery vehiclein three ways: by forming porous starting materials, by sprayingconsolidated starting materials with a porous coating, and by sprayingnear net-shaped medical devices with a porous coating. Current thermaland cold spray processes inherently include a degree of porosity thatare supplemented with post-processing techniques that provide fullconsolidation of the sprayed material. However, the present inventiontakes advantage of the spray process to create a desired level ofporosity so as to produce substrates and coatings that can elute a drug.The spray process may incorporate a wide variety of materials, such asmetals, metal alloys, polymers, ceramics, cermets and composites.Furthermore, the conditions of the spray process may be varied toachieve desired properties for a particular material, for example, tominimize oxidation or other contamination. In addition, the presentinvention provides for the manufacture of a medical device configuredfor drug delivery without the need for triple-coating the substrate witha polymer. Thus, a polymer topcoat may or may not be needed with porousmedical devices manufactured by spray processes of the presentinvention.

Hypotubing or other tube stock manufactured using the spray processes ofthe present invention may be configured into a stent or other tubularmedical device. The porous medical device may then be impregnated with atherapeutic agent or drug via known or to be developed transportmechanisms, such as soaking in a solution having an effectiveconcentration of the drug or agent. The spray process may be designed toprovide a multiple gradient of porosity through and/or within thematerial, e.g., denser on the outer diameter of a stent so the drugreleases preferentially into the artery wall, or denser then more porousthen denser again through the device thickness to allow the materialitself to act as a diffusion barrier for the release of the drug. Theprocess could also potentially spray different materials into thedifferent layers, so long as the corrosion and mechanical properties ofthe manufactured stent were not adversely affected. For example, thebase layer of the medical device could be metallic with an outer layerbeing formed from a sprayed ceramic, wherein either the base layerand/or the coating may be porous.

Alternatively, a spray process of the present invention may be used tocoat existing tube stock or starting materials for further processinginto a medical device, such as a stent. This inventive coating processhas the advantage that soaking the porous coated medical device in adrug would limit the drug coating to the outer diameter only of themedical device, thereby minimizing drug release into the bloodstream.The coating may be composed from a material of the same composition asthe underlying substrate or may be composed of a different material,such as a ceramic, that would not adversely affect the corrosion ormechanical functionality of the end product. One aspect of the presentinvention contemplates that the drug-eluting medical device is formed atleast in part of a metallic material, for example, iron, cobalt,platinum, titanium, and their alloys.

Another aspect of the present invention includes coating a nearnet-shaped medical device formed by conventional manufacturing methods.A coating formed by the spray process of the present invention may bemetallic, ceramic, or any other material that can undergo the thermal orcold spray process successfully. Such a coated medical device may beimpregnated with a therapeutic agent or drug via a known or to bedeveloped transport mechanism. A drug or agent that could withstand thetemperature/pressure of the spray process could be sprayed directly ontothe medical device with the coating material. A further aspect of thepresent invention includes using the spray process to form functionallygraded coatings so that the sprayed material acts as a controllingdiffusion barrier to drug release. The process may provide an all-overcoating or a coating focusing only on the outer diameter and sidewallsof the medical device, thereby allowing preferential focusing of thedelivery of a drug or therapeutic agent.

The therapeutic agents and drugs that may be loaded into thedrug-eluting porous medical device of the present invention can includeantiplatelets, anticoagulants, antifibrins, antiinflammatories,antithrombins, and antiproliferatives. Such drugs and agents are mostoften used to treat or prevent restenosis, and are provided by way ofexample and are not meant to be limiting, since other types oftherapeutic agents which are equally applicable for use with the presentinvention may be incorporated in a porous medical device formed by sprayprocessing.

Other features and advantages of the invention will become apparent fromthe following detailed description, taken in conjunction with theaccompanying drawings, which illustrate, by way of example, the featuresof the invention.

DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a schematic diagram of a spherical particle impinged ontoa flat substrate so at to create a splat.

FIG. 2 depicts a schematic diagram of a porous spray coating.

FIG. 3 depicts a schematic diagram of a porous spray coating containinga drug or therapeutic agent.

FIG. 4 depicts a schematic diagram of a cold spray processing apparatus.

FIG. 5 depicts a schematic diagram of a combustion wire thermal sprayprocessing apparatus.

FIG. 6 depicts a schematic diagram of a combustion powder thermal sprayprocessing apparatus.

FIG. 7 depicts a schematic diagram of an arc wire thermal sprayprocessing apparatus.

FIG. 8 depicts a schematic diagram of an HVOF thermal spray processingapparatus.

FIG. 9 depicts a schematic diagram of a plasma thermal spray processingapparatus.

FIG. 10 depicts a schematic diagram of a detonation thermal sprayprocessing apparatus.

FIG. 11 depicts a perspective view of an embodiment of a stent made inaccordance with the present invention.

FIG. 12 depicts a cross-sectional view along lines 12-12 of FIG. 11showing a coating made in accordance with the present invention.

FIG. 13 depicts an alternate view of FIG. 12, including an externallayer over the coating.

FIG. 14 depicts a perspective and exploded view of an unexpanded stentembodying the present invention.

FIG. 15 depicts a plan view of a flattened section of the stent shown inFIG. 14 so as to illustrate the undulating pattern of the stent.

FIG. 16 depicts a longitudinal plan view of an anastamosis device madein accordance with the present invention.

FIG. 17 depicts a longitudinal plan view of an embodiment of an expandedembolic protection device made in accordance with the present theinvention.

FIG. 18 depicts a perspective view of a graft assembly having aplurality of marker bands and attachment systems made in accordance withthe present the invention.

FIG. 19 depicts a schematic representation of equipment for lasercutting tube stock in the manufacture of a medical device made inaccordance with the present invention.

FIG. 20 depicts a longitudinal plan view of a stent delivery catheterassembly made in accordance with the present invention, wherein thestent has been positioned proximate to a lesion within a cross-sectionof a patient's blood vessel.

FIG. 21 depicts a longitudinal plan view of the distal end of a stentdelivery catheter assembly made in accordance with the presentinvention, wherein the balloon and stent are in an expanded state withina cross-section of a patient's blood vessel.

FIG. 22 depicts a longitudinal plan view of a stent made in accordancewith the present invention, wherein the stent has been expanded andremains within a cross-section of a patient's blood vessel.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to use of various spray processes forforming porous starting materials and porous near net-shaped medicaldevices, and to provide a porous coating on starting materials or nearnet-shaped medical devices. In accordance with the present invention,thermal spraying and/or cold spraying may be used to partially or whollyform starting materials, such as, but not limited to, tube stock,substrate sheets and wire, which can be further processed into anet-shaped (finished) medical devices. Similarly, thermal sprayingand/or cold spraying may be used to coat starting materials or to coatnear-net-shaped medical devices, such as, but not limited to, stents,anastomosis clips, embolic protection filters, graft attachment systems,markers, guide wires, mitral valve repair devices and defibrillator leadtips. As part of the spray process or as a separate aspect of the methodof manufacture of the medical device, a therapeutic agent or drug may beapplied to the porous coating or substrate. While virtually any medicaldevice that is implanted or used in the body will benefit from thepresent invention, the embodiments disclosed herein as applied to stentsare intended as only examples and are not meant to be limiting.

Spray processing (thermal spraying and cold spraying) provides methodsfor manufacturing a porous medical device for use as a drug deliveryvehicle in three ways: (1) creating porous tube stock (e.g., hypotubing)or other starting material via thermal or cold spraying; (2) sprayingpre-existing starting materials (e.g., tube stock or metallic sheets)with a porous coating; and (3) spraying pre-existing medical devices(e.g., stents) with a porous coating. The various spray processes canutilize a wide variety of materials, and the conditions of the processmay be varied depending on the material to minimize oxidation or othercontamination. As used herein, thermal spray processing refers to agroup of known metallurgical spray processes, such as, but not limitedto, combustion (wire and powder), arc wire, high velocity oxy-fuel(HVOF), plasma and detonation (see FIGS. 5-10). As used herein, coldspray processing refers to recently developed processes in which lowertemperatures and higher velocities (versus those used in thermal sprayprocessing) are used to impinge the material onto a substrate or mandrel(FIG. 4).

Both the processes of thermal spraying and cold spraying inherently haveporosity as a difficulty to overcome, and while current methods allow upto full (one-hundred percent) consolidation of the sprayed material, thepresent invention produces a porous coating or porous substrate that canelute a drug or therapeutic agent. A potential exists for drugco-spraying with the coating or substrate material, so long as the drugdoes not degrade at the high temperatures and/or velocities used in thespray process. As desired, a polymer or similar topcoat to protect orcontrol the release of the therapeutic agent or drug could be applied tothe medical device via a spray process, so long as the polymer would notdegrade from the processing.

Starting materials, such as tube stock (hypotubing) or substrate sheetsmay be manufactured using a spray process. The starting material maythen be processed into a medical device (stent), and the porous materialmay be impregnated with a therapeutic agent or drug via known or to bedeveloped transport mechanisms, such as soaking in or spraying with asolution having an effective drug or agent concentration. For purposesof the present invention, the term “impregnate” means to fill throughoutor to saturate. The spray process may be varied to allow a multiplegradient of porosity through and/or within the material, e.g., denser onthe inner diameter or layers (so the drug releases preferentially intothe artery wall for a stent), or denser—then more porous—then denseragain to allow the material itself to act as a diffusion barrier for therelease of the therapeutic agent or drug. The process could alsopotentially spray different materials into the different layers, so longas the corrosion and mechanical properties of the manufactured medicaldevice were not adversely affected. For example, the base layer(s) ofthe medical device could be formed from a metal or alloy, while theouter layer(s) of the medical device may be formed from a ceramicmaterial.

The spray process of the present invention may also be used to coatexisting starting materials for medical devices, such as tube stock,hypotubing and sheets of a substrate material for further processinginto a medical device, such as a stent. Use of a spray process has theadvantage that soaking the porous coated medical device in a therapeuticagent or drug would limit the drug or therapeutic agent to the outersurface of the medical device, minimizing release of the drug or agentinto the bloodstream. The coating may be made from a material of thesame composition of the underlying starting material (e.g., a metallicalloy), or may be made from other material (e.g., a ceramic) that wouldnot adversely affect the corrosion or mechanical functionality of theend product. As with forming starting materials, the spray process ofthe present invention could be used to produce functionally gradedcoatings (e.g., different degrees of density and porosity) so as toallow the coating material to create a diffusion barrier to control therelease of the therapeutic agent or drug.

The spray process of the present invention may be used to coat a nearnet-shaped medical device, such as an existing stent. Such a coatingcould be metallic, ceramic, composite, polymeric or any other materialthat can undergo the spray process successfully. The coated medicaldevice would then be impregnated with a drug or therapeutic agent viaknown or to be developed transport mechanisms. Alternatively, the drugor agent could be co-sprayed with the coating material, so long as thereis minimal resulting degradation. Thus, a therapeutic agent or drug thatcould withstand the temperature and pressure of the spray process couldbe applied directly onto the existing medical device with the coatingmaterial. A special fixture may be constructed to hold the medicaldevice and prevent damage during the coating process. As with coatingstarting materials, the spraying could be functionally graded to allowthe material to act as a controlling diffusion barrier to drug release.The spraying could consist of an all-over coating or a coating focusingonly on the outer surface or diameter of the medical device and anysidewalls when an inert material, such as a ceramic were used, allowingpreferential focusing of the drug delivery. For example, a stent madefrom 31 6L stainless steel could be layered with a porous coating of aceramic and then impregnated with paclitaxel. The drug coated stentcould then be further coated with a protective polymer layer.

As used herein, spray processing describes a broad class of relatedprocesses in which molten (or semi-molten) droplets or fine particles ofa metal, metal alloy, ceramic, glass, polymer and/or other suitablematerial are (1) sprayed to form a starting material (e.g., a tube stockor flat sheet); (2) sprayed onto a surface of a previously formedsubstrate material (e.g., hypotube or sheet metal) to produce a coating;or (3) sprayed onto a near-net-shape product. The spray process providesthe medical device with unique properties, such as strain-tolerantcomposites or porous materials susceptible to impregnation with atherapeutic agent or drug. Deposition rates via spray processes are veryhigh in comparison to alternative coating technologies, providingdeposit thicknesses commonly in the range of about 0.1 to 1.0 millimeter(mm). Furthermore, thicknesses greater than one centimeter (cm) can beachieved with some materials. Two types of spray process compatible withthe present invention include thermal spray processing and coldspraying.

Some advantages of using a spray process to form a porous medical deviceinclude the versatility with respect to feed materials (metals,ceramics, and polymers in the form of wires, rods, or powders); thecapacity to form barrier and functional coatings on a wide range ofsubstrates; the ability to create freestanding structures for net-shapemanufacturing of high performance ceramics, composites, and functionallygraded materials; and the rapid solidification synthesis of specializedmaterials. Further, the spray process can be used to manufacture a netor near net-shaped medical device, such that the product resulting fromthe spray process is close to or at the desired size and shape of thefinal product. Spray processing is presented here both with and withoutpost-processing of the sprayed material.

There are many possible variations of known spray process for formingporous starting materials and porous coatings resulting in medicaldevices of the present invention. Because porous starting materials andcoatings may be used in conjunction with medical devices that aregenerally cylindrical in shape, the spray processes may incorporateeither a moving spray gun and/or a moving mandrel or substrate so as touniformly disperse material onto the mandrel to form the porous startingmaterial or porous coating. The spray processes used in the presentinvention may be enhanced through the use of a precision computercontrolled apparatus.

Another benefit of using a spray process to manufacture a medical deviceis that the spray process may be used to form porous tube stock on topof a removable mandrel. The porous tube stock formed by a spray processcan be used in place of a gun drilled or extruded rod, and eliminatesthe need for subsequent tube manufacturing.

The thickness of the tube stock may be varied by spraying more or lessmaterial, and the inner diameter dimensions may be varied by changingthe size of the mandrel. The inner mandrel may be made of a substancethat melts out, or that is coated with a substance that allows easyremoval of the finished sprayed tube stock. If the grain size, porosity,and dimensional tolerances (including wall runout, wall thickness,concentricity and surface roughness) are within specifications, themandrel may be removed and the sprayed tube stock may subjected tofurther processing into a stent or other tubular or ring-shaped product.To create a ring-shaped product from a tube stock, the tube is sprayedto the desired dimensions and then cut in the transverse direction toresult in rings of the desired size.

For removal of the porous tube stock after it is formed, it may bebeneficial to either melt or shrink the mandrel's diameter to easeremoval of the tube stock. For example, the mandrel can be formed ofmetal that will shrink in diameter when cooled, while the tube stock maybe heated so that it expands radially outwardly. The mandrel can then beeasily removed from the tube stock. The mandrel and tube stock may alsoboth be heated so that the difference in expansion rates may causeseparation between the two. The mandrel may also be removed from thetube stock by a process called “cross-rolling.” The tube stock, with themandrel inside, can be run through a series of crossed rollers that willflex the tube stock and impart a separation between the tube and themandrel, which is then easily removed. Alternatively, the mandrel couldbe lubricated so as to provide a low friction surface from which toslide the off tube stock.

Any of several known or to be developed post-processing operations maybe performed on a porous tube stock formed from a spray process so as toimprove or otherwise modify grain size, porosity, and final dimensionsand tolerances of the sprayed tube stock. The inner diameter dimensionsand surface finish of the porous tube stock may be dependant on themandrel that is used. If the starting size of the sprayed tube is largeenough, it may be desirous to bore and ream or just ream the innerdiameter for both dimension and surface roughness improvement. A drawingoperation may be performed on the sprayed tube to achieve the desiredfinal size. In addition, if the outer diameter is too rough, the tubestock may be machined or ground prior to the drawing operation. Further,the tube stock may be mechanically processed or swaged before the tubestock is removed from the mandrel in order to develop desired mechanicalproperties. After the tube stock is removed from the mandrel other postprocessing includes exerting high mechanical pressures onto the stent inorder to develop the desired mechanical properties and tempering andhardening the tube stock with traditional heat treating mechanisms knownin the art. For correct sizing, the outer diameter and/or the innerdiameter of the tube stock can be machined, reamed, ground, or drawn tosize after being removed from the mandrel. The grain size of the poroustube stock may be decreased by reducing the required number ofheat-processing steps or by reducing the starting size of the rawmaterial that is spray processed to form the tubing.

Any of several known or to be developed post-processing operations mayalso be performed on a porous coating formed on a medical device from aspray process so as to improve or otherwise modify grain size, porosity,and final dimensional tolerances of the sprayed medical device. Further,the thickness of the coating may be varied by spraying more or lessmaterial, and may be varied along the length and around the diameter ofthe object to be-coated. If a porous coating is formed by sprayprocessing the inner diameter of tube stock or other tubular nearnet-shaped devices (such as stents), then post-processing may includemodifying the inner diameter dimensions and surface roughness by, forexample, boring and/or reaming. If the porous coating is formed by sprayprocessing an outer wall or surface of the medical device,post-processing may include machining (e.g., centerless grinding) ordrawing to reduce coating thickness variability and to improve thesurface finish. When the grain or node size, material density, porosityand dimensional tolerances of the porous coating are within desiredspecifications, the porous coated medical device may be subjected topost-passivation or other desired post spray processing steps when thecoating process is an intermediate step in finishing the medical device.

While spray processing may be used to manufacture near-net shape medicaldevices, the variability in the spray process may requirepost-processing so that the product achieves the required dimensionaltolerances. Any of several known or to be developed post-processingoperations may be performed on a porous medical device formed from aspray process so as to improve or otherwise modify grain size, porosity,and final dimensional tolerances of the sprayed medical device. Suchprocessing may include machining, centerless grinding, heat treating orother surface processing of the outer wall or surface of the sprayedmedical device to reduce wall thickness variability and to improve thesurface finish.

Two aspects of using spray processing to create porous medical devicesof the present invention include (1) controlling the grain size of thesprayed material, and (2) controlling the degree of porosity in thesprayed substrate or coating.

The grain size or node size of the sprayed material used in porousstarting materials or sprayed porous coatings resulting from the presentinvention depends on numerous factors, including the size of theparticles being sprayed; the grain size of the particles; the formation,impact and rate of solidification of the sprayed particles; and thelength of time the particle material is heated above a temperature thatallows significant grain growth. Grain-size strengthening is where thereis an increase in strength of a material due to a decrease in the grainsize. A larger grain-boundary area resulting from smaller grain sizesmore effectively blocks dislocation movement. The type and amount ofworking required to achieve a desired grain size depends on the materialbeing sprayed, for example, ceramics may require a high temperatureworking step, and metals and composites may be workable at roomtemperature.

For a metallic tube, if the grain size is larger than desired, the tubemay be swaged to introduce heavy dislocation densities, then heattreated to recrystallize the material into finer grains. Alternatively,different material forms may be taken through a drawing or other workingand heat treating process to recrystallize the tubing. The outerdiameter of the tube usually requires a machining step to smooth thesurface after the swaging process, and the same may be true before thetubing can be properly drawn.

For a metallic coating, one modification to grain size that may be madeis to heat-treat the coating to control grain growth. For example, itmay be desirable to spray a metallic coating onto a target substrate,heat the coating, and then grow the metallic grains in the coating.Similarly, the porous coated substrate may be mechanically processed orswaged, annealed, heat-treated, or cross linked in order to developdesired mechanical properties. Generally, it is difficult to work aporous, coated substrate in a way that introduces a high dislocationdensity that may then be used to recrystallize the material. For a spraycoated metallic wire or tubing, the wire or tubing may be swaged ordrawn to produce a higher dislocation density, then annealed torecrystallize to a smaller grain size. Porous ceramic coatings formedfrom a spray process may require post-processing heating to controlgrain size; whereas, porous polymeric coatings may require furthercross-linking.

Lowering the grain size and increasing the number of grains across thethickness of the porous medical device allows the grains within themedical device to act more as a continuum and less as a step function.For example, spray processing 31 6L stainless steel to a smaller grainsize may result in an average grain size of between approximately oneand sixty-four microns, with a subsequent average number of grainsacross the strut thickness about eight or greater. With a wellcontrolled spray process, it is possible to reduce the average grainsize of a porous medical device formed from spray processed 31 6Lstainless steel to between one and ten microns.

The mechanics and chemistry of spray processing inherently results insmall voids (porosity) in the sprayed material. The porosity of thesprayed material may be maximized, minimized, eliminated or controlledto a desired level through adjustment of the spray process parameters,such as particle size, temperature, pressure, injection velocity andco-spraying with a binder material that may be subsequently removed. Inaddition, the porous medical device may be post-processed to furthercontrol the size and distribution of the pores and voids. One suchmethod of post processing to control porosity is to process the materialunder high mechanical pressure in a vacuum to sinter the grainstogether, as is generally used for powder processing. Additional methodsto control porosity include co-spraying with varying amounts of a bindermaterial that may be removed through subsequent operation, such assublimation or soaking in a solvent.

The process of manufacturing porous starting materials, porous coatingsand porous near net-shaped medical devices in accordance with thepresent invention requires selecting a spray process method andapparatus, such as cold spraying, combustion spraying, arc spraying,high velocity oxy-fuel spraying and plasma spraying. The spray processselected must be compatible with the material to be sprayed, such asmetals, alloys, polymers, ceramics, and cermets. Similarly, the same oran additional spray process could be selected for spraying of a drug ortherapeutic agent, such as antiplatelets, anticoagulants, antifibrins,anti-inflammatories, antithrombins, and antiproliferatives.

Referring to FIGS. 1-3, an aspect of each spray process includes forminga deposit 50 by directing a particle 52 of the source material towards amandrel or substrate 54. Depending on the spray process selected, theparticle may be in a molten, semi-molten or solid state. When theparticle contacts the mandrel or substrate, the particle tends toflatten to form a splat 56 (FIG. 1), which adheres or otherwise bonds tothe mandrel or substrate. The resulting spray deposit is generallycomposed of cohesively bonded splats, that result from the high velocityimpact, spreading, deformation and/or rapid solidification of a highflux of particles. The physical properties and behavior of the depositdepend on many factors, including the cohesive strength among thesplats, the size and morphology of the porosity, oxidation of thestarting material, the occurrence of cracks and defects within thedeposit, and the grain structure of the source material within thesplats. In addition, some rogue particles 58 may not form splats uponcontact with the substrate or newly formed splats and may generallyretain their original shape, e.g., spherical.

As shown in FIG. 2, the deposit 50 may be formed with considerable poresor voids 60, thereby creating a porous deposit in accordance with thepresent invention. The amount of voids or degree of porosity may becontrolled during the spray process or during post-processing steps asheretofore described. One or more drugs or therapeutic agents 62 may beapplied to the porous deposit by a variety of known or to be developedprocess, such a soaking or dipping the porous tube stock, substratesheet, medical device or the like in a solution or bath of the drug ortherapeutic agent. Similarly, the drug or therapeutic agent may besprayed on the coating after the spraying of the starting material or atthe same time as spraying the starting material (co-spraying). The sprayprocess for applying the drug or agent to the porous deposit may be oneof the spray processes described herein, or a lower temperature and/orreduced velocity (lower pressure) process so as to prevent or reducedegradation of the active ingredient in the drug or agent. The result ofthe present inventive method is a drug impregnated porous coating orsubstrate, as shown in FIG. 3.

Materials used in the spray process can include elements (e.g., metals),metallic alloys (e.g., iron-based, cobalt-based, titanium-based),ceramics, composites, cermets and polymers. Suitable biocompatiblematerials for use in forming medical devices using the spray process ofthe present invention include, but are not limited to, elements andalloys of titanium, tungsten, tantalum, vanadium, gold, silver,palladium, platinum and iridium. Certain biocompatible metal alloys thathave been used in forming medical devices include:

(1) iron-carbon alloys, e.g., ASTM F 138, ASTM P139, AISI 31 6L(18Cr-14Ni-2.5 Mb);

(2) cobalt-chromium alloys, e.g., ASTM F90 (Co-20Cr-20W-1ONi) [availableas trade name products HAYNES 25 (Haynes) and L-605 (Carpenter)], ASTMF562 (35Co-35Ni-2OCr-10Mo) [available as trade name product MP35N(SPSTechnologies)], ASTM F 1058 (4OCo-20Cr-16Fe-15Ni-7Mo) [available astrade name products ELGILOY (Elgin) and PHYNOX (Imphy Ugine Precision)],HAYNES 188 (Haynes) (Co-24Ni-23Cr-15W); and

(3) nickel-titanium alloys, e.g., ASTM F2063[nitinol available from WahChang and Special Metals].

Suitable biocompatible polymers that may be used in the spray process aspart of the substrate, coating or topcoat include, but are not limitedto polymethyl-methacrylate (PMMA), ethylenevinylalcohol (EVAL),polybutylmethacrylate (PBMA), biodegradable polymers [such aspolyglycolic acid (PGA) and polyL-lactic acid (PLLA)], copolymers andblends thereof.

Various therapeutic agents, drugs and other pharmacologic compounds maybe applied to the porous substrate or porous coating to control localthrombosis and restenosis. Classes of such compounds include, but arenot limited to, substances that are antiproliferative, antithrombogenic,antineoplastic, antiinflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antibiotic, and antioxidant.Specific examples of therapeutic agents or drugs that are suitable foruse in accordance with the present invention include taxol, paclitaxel,docetaxel, sirolimus, everolimus, actinomycin D (ActD), prostaglandins,aspirin or derivatives and analogs thereof.

Examples of antiplatelets, anticoagulants, antifibrins, andantithrombins include, but are not limited to, sodium heparin, lowmolecular weight heparin, hirudin, argatroban, forskolin, vapiprost,prostacyclin and prostacyclin analogs, dextran,D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole,glycoprotein Jib/lila platelet membrane receptor antagonist, recombinantbirudin, thrombin inhibitor (available from Biogen located in Cambridge,Mass.), and 7E-3B (an antiplatelet drug from Centocor located inMalvern, Pa.). Examples of antimitotic agents include methotrexate,azathioprine, vincristine, vinblastine, fluorouracil, adriamycin, andmutamycin.

Examples of cytostatic or antiproliferative agents include angiopeptin(a somatostatin analog from Ibsen located in the United Kingdom),angiotensin converting enzyme inhibitors such as CAPTOPRIL (availablefrom Squibb located in New York, N.Y.), CILAZAP'RIL (available fromHoffman-LaRoche located in Basel, Switzerland), or LISINOPR.IL(available from Merck located in Whitehouse Station, N.J.), calciumchannel blockers (such as nifedipine), colchicine, fibroblast growthfactor (“FGF”) antagonists, fish oil (omega 3-fatty acid), histamineantagonists, LOVA-STATIN (an inhibitor of HMG-CoA reductase, acholesterol lowering drug from Merck), methotrexate, monoclonalantibodies [such as platelet-derived growth factor (“PDGF”) receptors],nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitor(available from GlaxoSmithKline located in United Kingdom), seramin (aPDGF antagonist), serotonin blockers, steroids, thioprotease inhibitors,triazolo-pyrimidine (a PDGF antagonist), and nitric oxide. Othertherapeutic drugs or agents which may be appropriate includealpha-interferon, genetically engineered epithelial cells, anddexamethasone.

While the foregoing therapeutic agents have been used to prevent ortreat restenosis, they are provided by way of example and are not meantto be limiting, since other therapeutic drugs may be developed which areequally applicable for use with the present invention. The treatment ofdiseases using the above therapeutic agents are known in the art. Thecalculation of dosages, dosage rates and appropriate duration oftreatment are previously known in the art. Furthermore, the therapeuticdrugs or agents are applied to the porous substrate or coating or aspart of the spray process at desired concentration levels per methodswell known in the art.

As mentioned above, spray processing includes several variants of theapparatus and spraying method, such as cold spraying, combustionspraying, arc spraying, high velocity oxy-fuel spraying and plasmaspraying. The following is a brief summary of the basic components andfunctions of several of the spray processes that may be used tomanufacture porous starting materials, coatings and near net-shapedmedical devices in accordance with the present invention.

As shown in FIG. 4, cold spray processing provides a manufacturingprocess for expanding the operational window for coating and formingmedical devices from biocompatible materials that are deposited withmuch lower thermal exposure than encountered with traditional thermalspray processes. The cold spray process exploits properties of gasdynamics that permit supersonic gas streams and attendant particlevelocities to be obtained. In addition, the cold spray process permits ahigh degree of spatial control by virtue of the gas nozzlecharacteristics and generally short standoff distances that can beemployed. This results in a uniform structure of the coating orspray-formed substrate with a substantially preserved formation ofpowder material without phase transformations and hardening, i.e., thecoatings applied do not crack, and their corrosion resistance,microhardness, and cohesion and adhesion strengths are enhanced.

The cold spray process involves minimal heat input to the feedstockpowder or the substrate, thus making it possible to deposit thermallysensitive as well as conventional materials. The process generallyproduces high density, low residual stress deposits with low oxidecontents. When the cold spray process is used to produce a consolidatedcoating or substrate, an average grain size of between one andsixty-four microns may be achieved. Alternatively, the cold sprayprocess parameters may be controlled to produce porous coatings andsubstrates that are suitable as a drug delivery vehicle. In addition, arobust drug or therapeutic agent may be co-sprayed with thebiocompatible material.

Cold spray processing may be used to project biocompatible materialsonto a surface at relatively lower temperatures than used in thermalspray processing, and the materials typically are not sprayed in amolten or semi-molten state. Instead, the biocompatible material issprayed as powder particles, which are introduced from a feeder into ahigh pressure gas (1.5 to 2.5 MPa) where both the gas and particlesenter a supersonic nozzle or jet. The particle size may range from aboutone to sixty-four microns for consolidated spray coatings, and may bevaried to achieve a desired degree of porosity. The gas is typicallyheated to a temperature from about 380° to 420° Celsius. Suitable gasesfor creating a jet stream (300-1500 m/sec) with the powder particlesinclude, but are not limited to, air, nitrogen (N₂), oxygen (0₂), helium(He), argon (Ar), xenon (Xe), and carbon dioxide (CO₂). The jet streamis directed against a mandrel or substrate positioned about eight to tenmillimeters from the nozzle so as to coat the mandrel or substrate withparticle splats, as shown in FIGS. 1-3. Finally, the spray-formedsubstrate or coated medical device is removed from the mandrel or otherholding mechanism for further post-processing, as described herein.

Typical values for tensile adhesion of consolidated cold spray coatingsare in the range of 30-80 MPa (4.4-11.6 ksi), with porosities in therange of one to ten volume percent, deposit thicknesses ranging from tenmicrons to ten millimeters, deposition rates in the range of 0.0 10 toabout 0.080 m3 per hour, and deposition efficiencies in the range offifty to eighty percent. Several considerations when using a cold sprayprocess include the dependency of porosity on the ambient sprayenvironment, powder characteristics (e.g., particle size and sizedistribution), and thermal-spray parameters (e.g., powder level,gas-flow features, and spray distance). The spray environment will havea significant influence on, for example, the oxidation of metals,leading to greater porosity.

As shown in FIG. 5, combustion wire thermal spray processing includesspraying molten metal or other biocompatible material onto a surface toform a substrate or a coating. First, the material in wire form ismelted in a flame (oxyacetylene flame is the most common) and atomizedusing compressed air or other gas to form a fine spray. When theatomized spray contacts a prepared substrate or mandrel, the fine moltendroplets rapidly solidify and form the desired substrate or coating. Thetemperature of a target near net-shaped medical device can be maintainedrelatively low during processing, thereby avoiding damage, metallurgicalchanges and distortion to the substrate material. The parameters of thecombustion wire thermal spray process (e.g., temperature, particle size,and gas velocity) can be adjusted to control the porosity of thespray-formed substrate or coating.

As shown in FIG. 6, combustion powder thermal spray processing includesspraying molten material onto a mandrel or near a net-shaped medicaldevice to provide a spray-formed substrate or a coating. In combustionwire spray processing there is a wide range of materials that can beeasily processed into powder form, providing a larger choice ofcoatings. The process, however, is limited by materials with highermelting temperatures than the flame can provide or if the materialdecomposes on heating. The biocompatible powder is propelled and meltedinto the flame (most commonly oxy-acetylene or hydrogen) to form a finespray. When the spray contacts a prepared substrate material, the finemolten droplets rapidly solidify and form the desired substrate orcoating. The temperature of a target near net-shaped medical device canbe maintained relatively low during processing, thereby avoiding damage,metallurgical changes and distortion to the substrate material. Theparameters of the combustion powder thermal spray process (e.g.,temperature, particle size, and gas velocity) can be adjusted to controlthe porosity of the spray-formed substrate or coating. In addition, arobust drug or therapeutic agent able to withstand the high temperaturesused in the process may be co-sprayed with the biocompatible material.

Referring to FIG. 7, the arc wire spray process utilizes a pair ofelectrically conductive wires formed from a biocompatible material thatare melted by an electric arc created between the two wires. The moltenmaterial is atomized by compressed gas and propelled towards the surfaceof a mandrel or near net-shaped medical device. The molten particlesrapidly solidify on impact to create a spray-formed substrate orcoating. The temperature of a target near net-shaped medical device canbe maintained relatively low during processing, thereby avoiding damage,metallurgical changes and distortion to the substrate material. Theparameters of the arc wire thermal spray process (e.g., temperature,particle size, and gas velocity) can be adjusted to control the porosityof the spray-formed substrate or coating. Benefits from using the arcwire apparatus for spray processing include low capital investment,simplicity of operation, and high deposit efficiency. Benefits of arcspray substrates and coatings include high bond strength and density,low internal stresses, high thickness capability and high qualitymicrostructures.

As shown in FIG. 8, high velocity oxygen fuel (HVOF) thermal sprayprocessing is similar to the combustion powder spray process (FIG. 6),except that HVOF utilizes extremely high spray velocities. There are avariety of HVOF apparatus (guns) that use different methods to achievehigh velocity spraying. One system incorporates a high pressure,water-cooled combustion chamber and a long nozzle. Fuel (e.g., kerosene,acetylene, propylene and hydrogen) and oxygen are fed into the chamber,and the combustion produces a hot, high pressure flame that is forceddown a nozzle, thereby increasing its velocity. Biocompatible material(e.g., metals and metal alloys) in powder form may be fed axially intothe combustion chamber under high pressure or fed through the side of alaval type nozzle, where the pressure is lower. The gas and particlevelocity exiting an HVOF gun can be in excess of 2500 feet per second.Further, the gas temperature is usually very high, ranging from 2500° to4500° F. The velocity of the biocompatible material particles causesfriction through kinetic energy when the particles make contact with amandrel or the substrate of a near net-shaped medical device. Such highenergy can aid in the melting and adhesion of the particles to themandrel or device so as to deposit a spray-formed substrate or coating.

Another known HVOF system uses a simpler combination of a high pressurecombustion nozzle and an air cap. Fuel gas (e.g., propane, propylene orhydrogen) and oxygen are supplied at high pressure, and combustionoccurs outside the nozzle and within an air cap supplied with compressedair. The compressed air pinches and accelerates the flame, and acts as acoolant for the gun. Biocompatible material in powder form is fed athigh pressure axially from the center of the nozzle towards a mandrel ornear net-shaped medical device so as to deposit a spray-formed substrateor coating.

Benefits of HVOF include high particle velocity, low particletemperatures, and reduced time at temperature during the sprayingprocess, which reduces oxidation and degradation of the constituents.The temperature of a target near net-shaped medical device can bemaintained relatively low during processing, thereby avoiding damage,metallurgical changes and distortion to the substrate material. Theparameters of the HVOF spray process (e.g., temperature, particle size,and gas velocity) can be adjusted to control the porosity of thespray-formed substrate or coating. In addition, a robust drug ortherapeutic agent able to withstand the high temperatures and velocitiesused in the process may be co-sprayed with the biocompatible material.

Referring to FIG. 9, the plasma spray process involves spraying moltenor heat softened biocompatible material onto a mandrel or the substrateof a near net-shaped medical device to provide a porous spray-formedsubstrate or a porous coating. Biocompatible material in the form ofpowder is injected into a very high temperature plasma flame, where itis rapidly heated and accelerated to a high velocity. The hot materialimpacts on the mandrel or substrate surface and rapidly cools tosolidify and form the desired substrate or coating. The temperature of atarget near net-shaped medical device can be maintained relatively lowduring processing, thereby avoiding damage, metallurgical changes anddistortion to the substrate material. The parameters of the plasma sprayprocess (e.g., temperature, particle size, and gas velocity) can beadjusted to control the porosity of the spray-formed substrate orcoating. In addition, a robust drug or therapeutic agent compatible withthe plasma process may be co-sprayed with the biocompatible material.

The plasma spray apparatus (gun) may be constructed of a copper anodeand tungsten cathode, both of which may be water cooled. Plasma gas(e.g., argon, nitrogen, hydrogen, helium) flows around the cathode andthrough the anode, which is shaped as a constricting nozzle. The plasmais initiated by a high voltage discharge, which causes localizedionization and a conductive path for a direct current (DC) arc to formbetween cathode and anode. The resistance heating from the arc causesthe gas to reach extreme temperatures, dissociate and ionize to formplasma. Typically, plasma generation begins at 10,000 F, and most plasmaguns maintain an internal temperature between 15,000° F. and 30,000° F.The plasma exits the anode nozzle as a free or neutral plasma flame(i.e., plasma that does not carry electric current). When the plasma isstabilized and ready for spraying, the electric arc extends down thenozzle, instead of shorting out to the nearest edge of the anode nozzle.This stretching of the electric arc is a result of a thermal pincheffect.

Due to the tremendous heat generated with this thermal spray process,the plasma gun components must be constantly cooled with water toprevent the gun from melting. Water may be sent to the gun through thesame lines as electrical power. Small temperature changes in the coolingwater may affect the ability to produce high quality, plasma generatedspray coatings and substrates. Accordingly, a water chiller can be usedto help produce high quality porous medical devices. Cold gas around thesurface of the water-cooled anode nozzle, being electricallynon-conductive, constricts the plasma arc, raising its temperature andvelocity. Powder is fed into the plasma flame most commonly via anexternal powder port mounted near the anode nozzle exit. The powder isso rapidly heated and accelerated that spray distances can be on theorder of twenty-five to one hundred-fifty millimeters. Benefitsassociated with a plasma spray process include a high degree offlexibility, a large choice of substrate and coating materials, highproduction spray rates, and automation of the process.

As shown in FIG. 10, a detonation thermal spray apparatus (gun) isconfigured with an elongate water-cooled barrel having inlet valves forreceiving gases and biocompatible material as a powder. Oxygen and fuel(acetylene is the most common) are fed into the barrel along with acharge of powder. A spark is used to ignite the gas mixture, and theresulting detonation heats and accelerates the powder to supersonicvelocity down the barrel so as to impact on a mandrel or near net-shapedmedical device. A pulse of nitrogen is used to purge the barrel aftereach detonation. This detonation process is repeated many times asecond. The high kinetic energy content powder particles provide adeposit of a very dense and strong spray-formed substrate or coating.The parameters of the detonation thermal spray process (e.g.,temperature, particle size, fuel type) can be adjusted to control theporosity of the spray-formed substrate or coating. In addition, a robustdrug or therapeutic agent compatible with the detonation process may beco-sprayed with the biocompatible material.

Referring now to FIG. 11, and by way of example, the present inventionmay be incorporated into a stent or similar endoprosthesis 10. Such astent may be balloon expandable or self-expanding. Such stents may bemade of any suitable biocompatible material as heretofore described.Such a stent may be of a ring 12 and link 13 pattern or otherconfigurations, such as, but not limited to a zigzag design, a coildesign or tubular mesh design, as known in the art or to be determinedin the future. The stent may be formed from porous tube stock or poroussubstrate sheets using a spray process of the present invention.Similarly, the stent may be formed as a porous near net-shaped device.Alternatively, the stent may be manufactured from non-porous startingmaterials (e.g., consolidated tube stock) using conventional techniques,and then covered with a porous coating, using the materials and sprayprocesses described herein.

Referring to FIGS. 12 and 13, the stent 10 may include porous coating ordeposit 50 disposed on the outside of the base material or substrate 54.Alternatively, the porous deposition layer may be embedded between thebase layer and an outer layer 64 of the stent. The outer layer of thestent may be the same material as the base layer, or may be of anothermaterial, such as a more biocompatible metal, a polymer or a drugdelivery component. Further, the coating or deposition layer may beimpregnated with a drug or therapeutic agent. A modification after thecoating is applied may include varying the radial thickness of thecoating around the stent. Accordingly, the radial- thickness can eitherbe varied around the diameter or along the length of the stent.Alternatively, the coating thickness may be varied as part of the sprayprocess.

In one embodiment as shown in FIGS. 14 and 15, the stent 10 isconfigured with links 13 between adjacent radially expandable rings 12.Each pair of links on one side of a ring may be circumferentially offsetfrom the pair on the other side of the ring. Such a configurationresults in a stent that is longitudinally flexible in essentially alldirections. As best observed in FIG. 15, the rings may be in the form ofa serpentine pattern 30. The serpentine pattern may be configured with aplurality of U-shaped members 31, W-shaped members 32, and Y-shapedmembers 33, each having a different radius so that expansion forces aremore evenly distributed over the various members. Other stent patternscan be formed by utilizing the processes of the present invention, andthe embodiments illustrated in FIGS. 11-15 are by way of example and arenot intended to be limiting.

For use in coronary arteries, the stent diameter must be very small, sothe tube stock from which it is made must necessarily also have a smalldiameter. Typically, the stent has an outer diameter on the order ofabout 0.03 inch (0.75 mm) to about 0.06 inch (1.5 mm) in the unexpandedcondition, equivalent to the tubing from which the stent is made, andcan be expanded to an outer diameter of 0.10 inch (2.5 mm) or more. Thewall thickness of the tubing is about 0.002 inch (0.05 mm) to about 0.01inch (0.25 mm). As with the foregoing stent dimensions, all of themedical devices that can be formed utilizing the present invention canvary substantially in size and shape so that the disclosed dimensionsand shapes are representative examples only and are not meant to belimiting.

The spray process of the present invention may also be used to form ananastomosis device (clip) 40, as shown in FIG. 16. The body 42 and theattachment portions 44 of the device may be formed from spray-formedtube stock, wire or the like. Similarly, the anastomosis device may beformed as a spray-formed near net-shaped device. Alternatively the bodyand/or the attachment portions of the device may be coated using thespray processes and biocompatible materials disclosed herein. Further, adrug or therapeutic agent may be applied to a porous base material orcoating. Various shapes and configurations of anastomosis devices may beformed or coated in accordance with the present invention.

Referring now to FIG. 17, and by way of example, the present inventionmay be incorporated into an embolic protection device 70. Such a devicemay include a spray-formed filter assembly 72 and a spray-formedexpandable strut assembly 74. The embolic protection device may furtherinclude an elongate tubular member 80, within which may be disposed aspray-formed guidewire 82 for positioning the device within a corporeallumen. In accordance with the present invention, the embolic protectiondevice may include a plurality of marker bands 86, which may beconstructed from spray-formed material. The expandable strut assemblymay include struts 76, 78, which may be spray-formed in accordance withthe present invention. Alternatively the filter assembly, strutassembly, tubular member and/or guidewire may be coated using a sprayprocess as heretofore described. The entire embolic protection device orportions thereof may be made porous and/or impregnated with a drug ortherapeutic agent.

Referring now to FIG. 18, the spray-formed materials of the presentinvention may be incorporated into a bifurcated graft 90. Likewise, thespray-formed materials may be incorporated into a tubular graft (notshown). Such a graft includes DACRON, PTFE or other suitable flexiblematerial having an upper body 92, a first leg 93 and a second leg 94,wherein the legs are joined to the upper body. Such a configurationforms a “Y” or “pants leg” configuration. A plurality of closely spacedspray-formed or spray-coated markers 96 may be configured on the outsideof the first and second legs. Similarly, wider spaced spray-formed orspray-coated markers 98 may be configured on the inside of the legs ofthe bifurcated graft (or visa versa). Such markers may be formed from aporous and/or drug impregnated material as heretofore described, and maybe sewn, glued or otherwise bonded to the body and/or legs of the graft.

In many such grafts 90, such as those used for repairing an abdominalaortic aneurysm, the upper body may include a first attachment system100 positioned proximate an upper (wider) opening of the graft. Tubegrafts may contain a like attachment system at the lower openings of thegraft. Similarly, bifurcated grafts may include smaller attachmentsystems 102 positioned at the end of the legs and proximate the lower(narrower) openings of the graft. Such attachment systems may be ofvarious configurations, such as, but not limited to, a ring and linkdesign, a zigzag design, a coil design, a slotted tube design or atubular mesh design. As heretofore described regarding stents (FIGS.11-15), the attachment system may be made from a variety ofbiocompatible materials and may be spray-formed or coated using a sprayprocess. The attachment systems may be formed from a porous and/or drugimpregnated material as heretofore described.

The illustrative stent 10 of the present invention and similar medicaldevice structures can be made-in many ways. One method of making such astent is to cut tube stock or sheets of substrate formed according tothe method and devices of the present invention so as to remove portionsof the tube stock in the desired pattern for the stent, leavingrelatively untouched the portions of the tube stock that are to form,for example, the cylindrical rings 12 and links 13. Various processes offorming the desired stent pattern are available and are known in theart, such as, but not limited to, using laser or chemical etching,electronic discharge machining and stamping.

A machine-controlled laser system 20 may be used to cut a desiredpattern in a spray-formed or spray-coated tube stock 21, as illustratedschematically in FIG. 19 and as is known in the art. The tube stock mayput in a rotatable collet fixture 22 of a machine-controlled apparatus23 for positioning the tube stock relative to a laser 24. According tomachine-encoded instructions, the tubing is rotated and movedlongitudinally relative to the laser. The laser selectively removesmaterial from the tube stock by ablation, and a desired pattern is cutinto the tube stock as programmed in a computerized numeric controller(CNC) 25. After laser cutting, the near net-shaped stent 10 may besurface modified by a number of methods known in the art, including beadblasting, etching and electropolishing.

Cutting a fine structure, such as a stent 10, via a machine-controlledlaser 20 requires minimal heat input and the ability to manipulate thetube stock 21 with precision. It is also necessary to support the tubestock, yet not allow the tube stock to distort during the cuttingoperation. To achieve a relatively small geometry of a desired stentpattern formed with ring struts 12 and links 13 sized for humanvasculature, it is necessary to have very precise control of the laser'spower level, focused spot size and positioning of the laser cuttingpath, which is well known in the art.

Referring now to FIG. 20, a stent 10 manufacture by a spray process inaccordance with the present invention may be mounted onto a deliverycatheter 11. The delivery catheter may also be constructed fromspray-formed components, and typically has a distal expandable portionor balloon 14 for expanding the stent within an artery 15. Portions ofthe proximal end of such a catheter can be made of spray-formed metaltubing or metal wire. The balloon may be formed of suitable materialssuch as polyethylene, polyethylene terephthalate, polyvinyl chloride,nylon and ionomers such as SURLYN manufactured by the Polymer ProductsDivision of the Du Pont Company. Other polymers may also be used. Inorder for the stent to remain in place on the balloon during delivery tothe site of the damage within the artery, the stent is compressed ontothe balloon.

The delivery of the stent 10 is accomplished in the following manner.The stent is first mounted onto the inflatable balloon 14 on the distalextremity of the delivery catheter 11. The catheter-stent assembly isintroduced within the patient's vasculature in a conventional Seldingertechnique through a guiding catheter (not shown). A guidewire 18 isdisposed across the damaged arterial section, and then thecatheter/stent assembly is advanced over the guidewire within the arteryuntil the stent is directly within the target site. As stated, themanufacture of guidewires also will benefit from the spray processes ofthe present invention. While the drawing figures illustrate a rapidexchange (Rx) intravascular catheter and guidewire, medical devices ofthe present invention may be also used with an over-the-wire (OTW)intravascular catheter. Additionally, although a balloon expandablestent and associate catheter assembly are depicted, a self-expandingstent in combination with an appropriate alternative catheter assemblymay be used.

Once the stent 10 is positioned at the desired location, the balloon 14of the catheter 11 is expanded, forcing the stent against the wall ofthe artery 15, as illustrated in FIG. 21. While not shown in thedrawing, the artery may be expanded slightly by the expansion of thestent to seat or otherwise fix the stent to prevent movement. In somecircumstances, during the treatment of stenotic portions of an artery,the lumen of the artery may have to be expanded considerably in order tofacilitate passage of blood or other fluid through the vessel lumen.

The stent 10 serves to hold open the artery 15 after the balloon 14 isdeflated and the catheter 11 is withdrawn, as illustrated by FIG. 22.Due to the formation of the stent from an elongated tubular member, theundulating component of the rings 12 of the stent is relatively flat intransverse cross-section, so that when the stent is expanded, the ringsare pressed into the wall of the artery and, as a result, do notinterfere with the blood flow through the artery. Furthermore, theclosely spaced rings and links 13 provide uniform support for the wallof the artery and, consequently, are well adapted to hold open theartery. A porous stent containing one or more of the drugs andtherapeutic agents disclosed herein may be used to reduce thrombosisand/or restenosis of the target vessel.

While several particular forms of the invention have been illustratedand described, it will also be apparent that various modifications canbe made without departing from the scope of the invention.

1. A method of manufacturing a medical device, comprising: forming aporous component for a medical device, wherein the porous component isselected from a group consisting of a start substrate from which amedical device is manufactured, a near net-shaped device from which amedical device is manufactured, and a coating disposed over a medicaldevice, wherein forming the porous component is performed by a methodselected from a group consisting of cold spray process, combustion wirethermal spray process, combustion powder thermal spray process, arc wirespray process, high velocity oxygen fuel thermal spray process, anddetonation thermal spray process, and wherein, if the porous componentis a start substrate or near net-shaped device, the process furthercomprises forming a medical device from the start substrate or the nearnet-shaped device.
 2. The method of claim 1, with the proviso that theforming the porous component does not include a plasma process.
 3. Themethod of claim 1, wherein the medical device is a stent.
 4. The methodof claim 1, further comprising applying a drug to the medical device. 5.The method of claim 1, further comprising manufacturing the medicaldevice into a drug delivery stent.
 6. The method of claim 1, whereinforming the start substrate comprises forming a porous tube stock, asubstrate sheet or a wire.
 7. The method of claim 1, wherein forming thestart substrate comprises applying a material on a tubular mandrel toform a tube stock, followed by removing the mandrel once the tube stockis formed.
 8. The method of claim 7, wherein the removing the mandrelcomprises subjecting the mandrel and the tube stock to heat, such thatthe coefficient of expansion of the mandrel is different than thecoefficient of expansion of the tube stock allowing the mandrel to beremoved from within the tube stock.
 9. The method of claim 7, whereinthe mandrel is coated to allow removal of the mandrel from the tubestock.
 10. The method of claim 7, wherein the removing the mandrelcomprises shrinking the mandrel to allow the mandrel to be removed fromwithin the tube stock.
 11. The method of claim 1, wherein forming thestart substrate comprises applying a material on a tubular mandrel suchthat the mandrel melts out during the formation of the start substrate.12. The method of claim 1, wherein the porous component comprises ametallic material.
 13. The method of claim 1, wherein the porouscomponent comprises a ceramic material.